Dbf4-dependent kinase (DDK) promotes resection of DNA double strand breaks and repair via homologous recombination

Abstract

DNA double strand breaks (DSBs) can be repaired via different cellular mechanisms, with two types of repair: direct ligation-based mechanisms or recombination-based mechanisms, like homologous recombination (HR). Ligation-based mechanisms require little processing of the broken ends, while extensive processing via the nucleolytic degradation of the 5’-terminated broken strand (DNA end resection) is crucial to commit cells to recombination-mediated repair. HR makes use of a homologous template, preferentially the sister chromatid, to direct the repair of the DSB and is therefore upregulated in cell cycle phases where the sister chromatid is available. DNA end resection is upregulated in the same cell cycle phases as well and is under strict cell cycle control. Different resection proteins were shown to be activated during the cell cycle by cyclin-dependent kinase (CDK), in both yeast and human. However, CDK-phosphomimetic mutants of these factors does not seem to be able to bypass the cell cycle regulation of DNA end resection. This suggests that additional cell cycle kinases might be important for this regulation. [...]